A new GABA-A receptor subtype coupled with Ca++/Cl- synporter modulates aminergic release from rat brain neuron terminals.
The aim of the present study was to give a better characterization of GABA receptors that modulate aminergic release. GABA or muscimol (15 microM) increased basal noradrenaline (3H-NA) release but reduced the following K+-evoked 3H-NA release in the synaptosomes from rat cerebellar cortex. Bicuculline and picrotoxin counteracted these two effects. The same GABA modulation resulted to operate also on dopaminergic and serotoninergic neuron terminals. The increased basal noradrenaline release resulted to be both calcium and chloride dependent and associated with an increased entry of 45Ca++ into the synaptosomes. We therefore advance the hypothesis of an involvement of a Cl-/Ca++ synporter system coupled to the receptor. Baclofen also reduced the K+-evoked 3H-NA release, but did not increase basal 3H-NA release; moreover, the interaction of baclofen G with GABA-B receptors resulted to be associated with the inhibition of 45Ca++ entry into synaptosomes. GABA-B receptors resulted to be present also on serotoninergic but not on dopaminergic neuron terminals. The GABA-C receptor agonist cis-4-aminocrotonic acid (CACA) did not influence either basal or K+-evoked 3H-NA release. These results point to a new type of GABA functional role through a different A-family receptor subtype, coupled with calcium influx in aminergic neuron terminals, modulating aminergic release.
Cerrito
F
F
Department of Experimental Medicine, University of L'Aquila, Italy.
Aloisi
G
G
Arminio
P
P
Fanini
D
D
D000818:Animals; D001481:Basal Metabolism; D001679:Biogenic Amines / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000493:pharmacokinetics*; D002525:Cerebellar Cortex / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002712:Chlorides / Q000493:pharmacokinetics*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001679:Biogenic Amines; D002712:Chlorides; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine